Normal function of the airway tree is to permit the free flow of gas to an from the alveoli. With inflammation, obstruction of these airways may occur that leads to severe difficulty in breathing or even death. This program project will focus on mechanisms by which allergic inflammation can alter the responsiveness of airways. Although both of these factors have been well studied independently, how they interact remains poorly understood. Inflammation can clearly have several independent and perhaps unrelated influences on the responsiveness of the airways. Of the many possible factors and processes that might be involved in the interaction of airway size and inflammation, we have chosen to focus on several where new insights will likely be obtained. These include the physical interaction between inflamed airways and parenchyma, the inflammatory cell and structural profile induced by specific cytokines regulation of perfusion and inflammatory cell traffic by the airway circulation, and altered neural sensitivity and control. Each project in this program will focus on one or more of these factors addressing several specific aims with state-of-the-art-approaches. Projects and methods span the range from subcellular and molecular approaches to quantitative measurements of airway size in vivo. Projects are tightly interactive with all project leaders serving as co-investigators on other projects, and frequent group meetings. These interactions not only facilitate the progress of work within each project, but they also enhance the development of new ideas and interactions between the projects. In this way the program project function to greatly enhance the productivity of individual progress, thereby making the composite endeavor far greater than the sum of the individual projects. Successful completion of the aims of this tightly integrated program will provide new insights into how airways function in an inflammatory environment.